Apheresis is a procedure in which individual blood components can be separated and collected from whole blood temporarily withdrawn from a subject. Typically, whole blood is withdrawn through a needle inserted into a vein of the subjects arm and into a cell separator, such as a centrifugal bowl. Once the whole blood is separated into its various components, one or more of the components can be removed from the centrifugal bowl. The remaining components can be returned to the subject along with optional compensation fluid to make up for the volume of the removed component. The process of drawing and returning continues until the quantity of the desired component has been collected, at which point the process is stopped. A central feature of apheresis systems is that the processed but unwanted components are returned to the donor. Separated blood components may include, for example, a high density component such as red blood cells, an intermediate density component such as platelets or white blood cells, and a lower density component such as plasma.
Among various blood component products obtainable through apheresis, the demand for platelet products is rapidly growing. This is particularly because, with the improvement in cancer therapy, there is a need to administer more and more platelets to patients with lowered hemopoietic function. Platelets are fragments of a large cell located in the marrow called a megakaryocyte and primarily contribute to hemostasis by performing the aggregation function. Platelets also have a role in tissue healing. Normal platelet counts are 150,000-400,000/mm3 in the adult. Platelet counts under 20,000/mm3 can cause various problems such as spontaneous bleeding.
Platelets have a short half-life of 4-6 days and the number of donors is limited. Therefore, in producing plasma reduced platelet products, it is important to harvest platelets from the whole blood supplied by a donor at a maximum yield and in a required amount. Further, it is known that the contamination of plasma reduced platelet product by white blood cells can lead to serious medial complications, such as GVH reactions. Therefore, it is also very important to keep the level of contamination by white blood cells as low as possible, while efficiently collecting platelets.
To that end, various techniques have been developed. For example, using “surge” technology, after whole blood is collected and concentrically separated within a centrifuge into higher density, intermediate density and lower density components and plasma is harvested (so-called “draw” step), the plasma is supplied through the centrifuge at a surge flow rate, that is, a flow rate that increases with time. By performing the surge, platelets can be preferentially displaced from the intermediate density components, which exist as a buffy coat mainly comprising a mixture of platelets and white blood cells. Plasma reduced platelet products can thereby be produced at an increased yield.
Instead of using surge technology, the platelet layer can also be extracted from the centrifuge by means of a layer “push” in which anticoagulated whole blood is introduced into the bowl until the platelet layer is pushed out, or by using a combination of surge and push methodologies. After harvesting a desired component or components, the residual blood components mostly comprising red blood cells are returned to the donor (so-called “return” step).
Typically, 450-500 ml of whole blood is processed during one cycle which comprises the above-mentioned successive steps. This amount is based on 15% or less of the total amount of blood in humans and, if more than this amount is taken out of the body at once, the donor may suffer from blood pressure lowering or dizziness. Using surge technology, the concentration of the sequestered platelet product ranges from 0.8×106/μL to 2.6×106/μL (typically 1.5×106/μL), with moderate leukocyte concentration. Pushed platelet product concentration tends to be higher but leads to greater leukocyte and red blood cell residual contamination.
This resulting platelet concentration is often too low for platelet product compatibility with arising pathogen inactivation methods. Additionally, simultaneous plasma collection of one to two additional plasma units may be prevented due to the relatively high volume of plasma captured with the platelet product. The relatively high plasma protein content in the platelet product is also less desirable in terms of recipient tolerance.
Blood processing systems, such as blood apheresis systems, add a citrated anticoagulant such as ACD-A to prevent blood and blood component clumping and coagulation within the system. Typically, the anticoagulant is mixed with the whole blood drawn from the donor. The ratio of anticoagulant to whole blood must be kept below a certain threshold because most of the anticoagulant introduced into the system will be returned to the donor. If too much anticoagulant is returned to the donor, the donor may experience adverse reactions such as a citrate reaction.